Dataset Information

Serum squamous cell carcinoma antigen as an early indicator of response during therapy of cervical cancer.

ABSTRACT:

Background

Pretreatment serum squamous cell carcinoma antigen (SCCA) is a prognostic biomarker in women with cervical cancer. SCCA has not been evaluated as an early indicator of response to chemoradiation therapy (CRT). The molecular role of the two SCCA isoforms, SCCA1 (SERPINB3) and SCCA2 (SERPINB4), in cervical cancer is unknown. We hypothesised that changes in serum SCCA during definitive CRT predicts treatment response, and that SCCA1 mediates radiation resistance.

Methods

Patients treated with definitive CRT for cervical squamous carcinoma with serum SCCA measured were included. SCCA immunohistochemistry was performed on tumour biopsies. Post-treatment FDG-PET/CT, recurrence, and overall survival were recorded. Radiation response of cervical tumour cell lines after SCCA1 expression or CRISPR/Cas9 knockout was evaluated by clonogenic survival assay.

Results

Persistently elevated serum SCCA during definitive CRT was an independent predictor of positive post-therapy FDG-PET/CT (P=0.043), recurrence (P=0.0046) and death (P=0.015). An SCCA1-expressing vector increased radioresistance, while SCCA knock out increased radiosensitivity of cervical tumour cell lines in vitro.

Conclusions

Early response assessment with serum SCCA is a powerful prognostic tool. These findings suggest that escalation of therapy in patients with elevated or sustained serum SCCA and molecular targeting of SCCA1 should be considered.

SUBMITTER: Markovina S

PROVIDER: S-EPMC5765231 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Serum squamous cell carcinoma antigen as an early indicator of response during therapy of cervical cancer.

Markovina Stephanie S Wang Songyan S Henke Lauren E LE Luke Cliff J CJ Pak Stephen C SC DeWees Todd T Pfeifer John D JD Schwarz Julie K JK Liu Weijun W Chen Shuai S Mutch David D Wang Xiaowei X Powell Matthew A MA Siegel Barry A BA Dehdashti Farrokh F Silverman Gary A GA Grigsby Perry W PW

British journal of cancer 20171107 1

<h4>Background</h4>Pretreatment serum squamous cell carcinoma antigen (SCCA) is a prognostic biomarker in women with cervical cancer. SCCA has not been evaluated as an early indicator of response to chemoradiation therapy (CRT). The molecular role of the two SCCA isoforms, SCCA1 (SERPINB3) and SCCA2 (SERPINB4), in cervical cancer is unknown. We hypothesised that changes in serum SCCA during definitive CRT predicts treatment response, and that SCCA1 mediates radiation resistance.<h4>Methods</h4>P ...[more]

PMID: 29112685

Similar Datasets

Project description:BackgroundTo investigate the prognostic role of pretreatment squamous cell carcinoma antigen (SCCA) in early-stage cervical cancer (CC).MethodsWe enrolled 487 cases of pathology-proven early-stage [International Federation of Gynecology and Obstetrics (FIGO) I/II] squamous or adenosquamous CC that were treated from 2012 to 2015. Restricted cubic splines (RCS) with a full Cox regression model were used to evaluate the association between SCCA levels and survival outcomes. Recursive partitioning analysis (RPA) was used to construct a risk stratification model for overall survival (OS). The performance of the RPA-based model was assessed using a receiver operating characteristic (ROC) curve.ResultsRCS analysis revealed an association between SCCA and OS and disease-free survival (DFS); SCCA ⩾2.5 ng/mL was robust for risk discrimination in our cohort. SCCA had an interaction effect with FIGO classification: Patients with FIGO I and SCCA ⩾2.5 ng/mL overlapped with those with FIGO II and SCCA < 2.5 ng/mL for OS [hazard ratio, 1.04 (95% confidence interval (CI): 0.49-2.24), p = 0.903] and DFS [1.05 (0.56-1.98), p = 0.876]. RPA modeling incorporating SCCA (<2.5 ng/mL and ⩾2.5 ng/mL) and FIGO classification divided CC into three prognostic groups: RPA I, FIGO stage I, and SCCA < 2.5 ng/mL; RPA II, FIGO stage I, and SCCA ⩾ 2.5 ng/mL, or FIGO stage II and SCCA < 2.5 ng/mL; and RPA III, FIGO stage II, and SCCA ⩾ 2.5 ng/mL; with 5-year OS of 94.0%, 85.1%, and 73.5%, respectively (p < 0.001). ROC analysis confirmed that the RPA model outperformed the FIGO 2018 stage with significantly improved accuracy for survival prediction [area under the curve: RPA versus FIGO, 0.663 (95% CI: 0.619-0.705] versus 0.621 (0.576-0.664), p = 0.045]. Importantly, the RPA groupings were associated with the efficacy of treatment regimens. Surgery followed by adjuvant treatment had a higher OS (p < 0.01) and DFS (p = 0.024) than other treatments for RPA III, whereas outcomes were comparable among treatment regimens for RPA I-II.ConclusionHerein, the role of SCCA for prognostication was confirmed, and a robust clinicomolecular risk stratification system that outperforms conventional FIGO classification in early-stage squamous and adenosquamous CC was presented. The model correlated with the efficacy of different treatment regimes.

Project description:BackgroundThe evaluation of the treatment response after concurrent chemotherapy and radiotherapy (CCRT) for locally advanced cervical cancer is closely related to the formulation of treatment strategies. Magnetic resonance imaging (MRI) is a recommended method for efficacy evaluation; however, a unified consensus has not yet been reached on its use, and it has its limitations. This study aimed to evaluate the diagnostic value of a combination of contrast-enhanced ultrasound (CEUS) parameters and the squamous cell carcinoma antigen (SCC-Ag) to establish another efficient and feasible examination method.MethodsThe data of 94 patients with cervical cancer who underwent transvaginal contrast-enhanced ultrasound (TV-CEUS) from October 2020 to March 2023 were retrospectively collected. Based on the inclusion and exclusion criteria, 70 patients diagnosed with cervical squamous cell carcinoma (SCC) who underwent CCRT were selected for inclusion in the study. The patients were divided into the residual disease (RD) group (comprising 26 patients) and the complete response (CR) group (comprising 44 patients) according to the diagnostic standard. Data on the grayscale echogenicity, color Doppler flow imaging (CDFI), CEUS parameters, and the SCC-Ag of all the patients were collected by two experienced radiologists. Inter-observer reliability was assessed using the intraclass correlation coefficient (ICC). Receiver operating characteristic (ROC) curves were created based on the non-parametric U-test or t-test results for the two groups. Delong's test was used to compare the area under the curve (AUC) between different ROC curves. A subgroup analysis was conducted based on the patient's age, tumor diameter, and disease stage.ResultsThe ICCs between the two observers ranged from 0.915 and 0.947. Hypervascular hyper-enhancement in the arterial phase, hypo-enhancement in the venous phase, and the SCC-Ag differed significantly between the RD and CR groups (P<0.05). The AUC of the ROC curve combining these indicators was 0.890 [95% confidence interval (CI): 0.792-0.989], which was higher than the AUC of any indicator alone (P<0.05). The subgroup analysis showed that the AUCs of the patients aged ≥53 and <53 years were 0.922 (95% CI: 0.816-1.00) and 0.896 (95% CI: 0.782-1.00), respectively, those of the patients with stage II, III, and IV were 0.881 (95% CI: 0.732-1.00), 0.955 (95% CI: 0.894-1.00), and 1.000 (95% CI: 1.00-1.00), respectively, and those of the patients with a tumor diameter ≤10 mm, 10 mm < tumor diameter (post) <20 mm, and tumor diameter (post) ≥20 mm were 0.976 (95% CI: 0.910-1.00), 0.883 (95% CI: 0.763-1.00), and 1.00 (95% CI: 1.00-1.00) respectively.ConclusionsTransvaginal ultrasound (TVUS), TV-CEUS, and the SCC-Ag can be used in combination to evaluate the patient response to CCRT in locally advanced cervical SCC. This integrated approach enhanced the accuracy of the diagnosis of residual lesions and may be helpful in treatment plan optimization.

Project description:There are currently no reliable, established serum biomarkers to predict the prognosis of radiotherapy for advanced cervical cancer. We aimed to identify serum biomarkers for survival after radiotherapy for cervical cancer. In this multicenter prospective cohort study, the usefulness of pre- and posttreatment serum protein levels of potential biomarkers, including squamous cell carcinoma antigen (SCC-Ag), apolipoprotein C-II (ApoC-II), matrix metalloproteinase (MMP)1, and MMP2, were evaluated together with clinical factors in 145 cervical cancer patients in order to determine their suitability to predict survival. Progression-free survival (PFS) was the primary endpoint, and overall survival (OS), pelvic PFS (PPFS), and distant metastasis-free survival (DMFS) were the secondary endpoints. Blood samples were collected before and 1 month after radiotherapy to measure serum biomarker levels. ApoC-II was measured using a monoclonal antibody-based enzyme-linked immunosorbent assay, which was developed for this purpose. Kaplan-Meier method, log-rank test, and univariate and multivariate Cox proportional hazards models were used for statistical analyses. In multivariate analysis, larger tumor size was independently associated with shorter PFS, OS, PPFS, and DMFS, while longer overall treatment time was independently associated with shorter PPFS. Higher pretreatment SCC-Ag (P < 0.001) was associated with shorter DMFS. Higher posttreatment SCC-Ag (P = 0.017) was also associated with shorter DMFS. Pretreatment ApoC-II was associated with PPFS in univariate analysis (P = 0.048), but not in multivariate analysis. Patients with pretreatment ApoC-II levels ≤ 25.8 μg/ml had shorter PPFS than those with pretreatment ApoC-II levels > 25.8 μg/ml (P = 0.023, log-rank test). Pre- and posttreatment serum SCC-Ag and pretreatment serum ApoC-II levels may be important biomarkers to predict survival outcomes of patients with cervical cancer after radiotherapy. Pre- and posttreatment SCC-Ag and pretreatment ApoC-II might be useful in clinical settings for screening patients to improve treatment strategies in cervical cancer.

Dataset Information

Serum squamous cell carcinoma antigen as an early indicator of response during therapy of cervical cancer.

Background

Methods

Results

Conclusions

Publications

Serum squamous cell carcinoma antigen as an early indicator of response during therapy of cervical cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets